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Biomedical subjects

Daniel L Hamilos

Publications and source records attributed to Daniel L Hamilos.

15 recordsLinked to original sources
PubMed2006

Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells.

Epithelial cells play an important role in orchestrating mucosal immune responses. In allergic-type inflammation, epithelial cells control the recruitment of eosinophils into the mucosa. Th2-type cytokine-driven release of eosinophil-active chemokines from epithelial cells directs eosinophil migration into the mucosal epithelium. CCR3, the main eosinophil chemokine receptor, regulates this process; however, the respective contribution of individual CCR3 ligands in eosinophil transepithelial migration is less well understood. Using an in vitro transepithelial chemotaxis system, we found that eotaxin-3 produced by IL-4-stimulated airway epithelial cells and CCR3 on eosinophils exclusively mediate eosinophil transepithelial migration. Eotaxin-3 protein levels were also increased in the nasal mucosal epithelium recovered from allergic patients as compared to non-allergic patients. Surprisingly, eotaxin-3 in IL-4-stimulated airway epithelial cells was predominantly cell surface bound, and the cell surface form was critical for eosinophil transepithelial migration. Eotaxin-3 cell surface association was partially glycosaminoglycan (GAG) dependent, but was completely protein dependent, suggesting that eotaxin-3 associates with both GAG and cell surface proteins. We thus provide evidence that cell surface-associated eotaxin-3 is the critical IL-4-dependent chemotactic signal mediating eosinophil transepithelial migration in the setting of allergic inflammation.

Blotting, Northern↗
PubMed2006

Rhinosinusitis: developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗
PubMed2006

Rhinosinusitis: Developing guidance for clinical trials.

The Rhinosinusitis Initiative was developed by 5 national societies. The current guidance document is an expansion of the 2004 publication, "Rhinosinusitis: Establishing definitions for clinical research and patient care" and provides templates for clinical trials in antimicrobial, anti-inflammatory, and symptom-relieving therapies for the following: (1) acute presumed bacterial rhinosinusitis, (2) chronic rhinosinusitis (CRS) without nasal polyps, (3) CRS with nasal polyps, and (4) classic allergic fungal rhinosinusitis. In addition to the templates for clinical trials and proposed study designs, the Rhinosinusitis Initiative has developed 6 appendices, which address (1) health outcomes, (2) nasal endoscopy and staging of CRS, (3) radiologic imaging, (4) microbiology, (5) laboratory measures, and (6) biostatistical methods.

Chronic Disease↗
PubMed2006

Ultrarush venom desensitization after systemic reactions during conventional venom immunotherapy.

BACKGROUND: Rush and ultrarush venom immunotherapy (VIT) protocols are safe and effective in patients with Hymenoptera hypersensitivity. However, these protocols have typically been used instead of conventional VIT and not in patients who have experienced adverse reactions during conventional VIT. To date, there are no reports of using an ultrarush VIT protocol to desensitize patients with a history of severe systemic reactions during conventional VIT. OBJECTIVE: To determine whether ultrarush VIT can be safely administered to a high-risk patient with a history of severe systemic reactions to conventional VIT. METHODS: Premedication with 40 mg of prednisone, 180 mg of fexofenadine, and 150 mg of ranitidine orally twice daily was initiated. The patient received VIT to mixed vespid and wasp in a medical intensive care unit via a 13-step buildup on day 1 followed by a 2-step buildup on day 2. Immunotherapy was begun with a dose of 0.005 microg of mixed vespid and 0.002 microg of wasp venom and achieved a total dose of 300 microg of mixed vespid and 100 microg of wasp venom. RESULTS: The patient tolerated the procedure with minimal adverse effects. She subsequently received maintenance dosing in the outpatient clinic weekly for 4 weeks and bimonthly for 8 weeks, and she continues monthly maintenance VIT. CONCLUSIONS: We report the first successful use of ultrarush VIT in a high-risk patient with a history of severe systemic reactions during conventional VIT. This protocol should be considered in patients with a history of allergy to vespids or wasps who require VIT but cannot reach a maintenance dose with conventional VIT owing to systemic reactions.

Adult↗
PubMed2005

Current thinking on the relationship between rhinosinusitis and asthma.

An observation made initially on clinical grounds and epidemiologic evidence, i.e., that rhinosinusitis and asthma are closely linked diseases is now supported by a growing body of scientific evidence. Most recent evidence supports the characterization of rhinosinusitis and asthma as two compartmental expressions of a common mucosal susceptibility to exogenous stimuli. In addition, there is evidence that the compartmental processes can affect and amplify each other via a systemic intermediary. The bone marrow is involved in this process, and IL-5 may be a key cytokine for orchestrating the systemic interaction. These facts argue that rhinosinusitis and asthma are not simply localized disease processes but part of a systemic inflammatory disease affecting the respiratory tract. They also provide a compelling rationale for combined treatment strategies with consideration of the treatment of rhinosinusitis as a means of improving asthma control and monitoring for signs of bronchial involvement in those with rhinosinusitis.

Asthma↗
PubMed2004

Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway.

We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 days with inhaled fluticasone propionate (1,760 microg/day) followed by a withdrawal period that lasted until peak expiratory airflow decreased by 25% and FEV(1) by 15% or 6 weeks elapsed. After glucocorticoid withdrawal, 13 of 25 subjects reached the target, whereas 12 subjects did not. The number of eosinophils in bronchial biopsies was increased by glucocorticoid withdrawal in both groups, but increases in airway T cells were found in only those with exacerbation. T-cell accumulation was a reflection of similar increases in both CD4(+) and CD8(+) T cells and was accompanied by increased expression of chemokine CCL5 (regulated upon activation, normal T cell expressed and secreted) in the airway epithelium without activation of the transcription factor nuclear factor-kappaB. The pattern of glucocorticoid-sensitive inflammation during an asthma exacerbation is more reminiscent of an antiviral response than an eosinophil-predominant response to allergen and implies an independent role for airway T cells in mediating asthma flares and in determining glucocorticoid efficacy in the treatment of this disease.

Adult↗
PubMed2004

Etiology of chronic rhinosinusitis: the role of fungus.

Chronic rhinosinusitis is an inflammatory disorder with numerous predisposing factors, including genetics, pollution, anatomic anomalies, bacteria, and fungus. In some studies, fungi have been cultured from nearly 100% of patients with rhinosinusitis and nasal polyposis. T-cell sensitization to fungus with production of the T-helper 2 (Th2) cytokine interleukin-5 has been proposed as a key step in the initiation of the disease. Interleukin-5 also plays an important role in the effector phase of the disease through its effects on eosinophilopoesis and eosinophil survival. There is considerable controversy concerning the role of fungi as the cause of "chronic eosinophilic rhinosinusitis" and whether this even represents a distinct clinical entity. Further study is also required to define the optimal treatment for the disease.

Animals↗
PubMed2003

IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate.

OBJECTIVES/HYPOTHESIS: Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features. STUDY DESIGN: Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression. METHODS: Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means. RESULTS: Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance. CONCLUSION: NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP.

Adult↗
PubMed2003

Causative and contributive factors to asthma severity and patterns of medication use in patients seeking specialized asthma care.

STUDY OBJECTIVES: (1) To assess the prevalence of specific factors considered causative or contributive to asthma in a population of patients seen in a specialized asthma clinic, and to determine whether any of these factors were associated with more severe disease; and (2) to assess the utilization of inhaled steroids by asthma severity in this population and compare it with published guidelines of the National Heart, Lung, and Blood Institute (NHLBI). DESIGN, SETTING, AND PATIENT POPULATION: We conducted a retrospective chart review of new patients seen in a specialized asthma treatment center over a 2.5-year period and recorded the prevalence of 14 causative or contributive factors, the severity of asthma, and the intensity of treatment with inhaled corticosteroids in each patient. Patients were grouped as mild asthma vs moderate/severe asthma and compared by chi(2) analysis and stepwise logistic regression to determine whether certain factors were associated with more severe asthma. MEASUREMENTS AND RESULTS: The average number of factors recorded was 2.9 +/- 1.8 in the mild group (+/- SD) and 3.5 +/- 1.6 in the moderate/severe asthma group. This difference was statistically significant (p = 0.014). Increasing age, male gender, symptomatic gastroesophageal reflux disease (GERD), and chronic sinusitis were independently associated with more severe asthma. Suboptimal use of inhaled corticosteroids was more common in patients with mild persistent asthma, but suboptimal dosing of inhaled corticosteroids was equally common in mild and moderate/severe asthma. No relationship was found between allergen sensitization combined with exposure to cats, dogs, dust mite, or molds and more severe asthma. CONCLUSIONS: This study confirms earlier studies showing that symptomatic GERD and chronic sinusitis are important comorbid conditions in patients with asthma, both being associated with greater asthma severity. This study further shows that the doses of inhaled corticosteroids used for treatment of asthma fall short of NHLBI guidelines in the majority of patients regardless of asthma severity.

Administration, Inhalation↗
PubMedDate not supplied

A retrospective analysis of treatment outcomes and time to relapse after intensive medical treatment for chronic sinusitis.

BACKGROUND: Despite the high prevalence of chronic sinusitis, there are few published studies assessing its response to medical treatment. We analyzed, retrospectively, 40 patients seen in our center who were treated for chronic sinusitis with a protocol of intensive medical therapy. Both symptomatic and radiographic improvements were assessed as well as factors associated with early relapse. METHODS: Intensive medical treatment consisted of 1 month of antibiotics, a short course of oral steroids, and adjunctive therapy (e.g., nasal irrigations plus intranasal steroids). After intensive medical therapy, adjunctive medical therapy was continued. A sinus computed tomography was performed at baseline and 6-8 weeks later and scored for extent of disease. Pre- and posttreatment symptom scores also were assessed. Time to relapse was defined as the time interval after antibiotic treatment at which a recurrence of symptoms necessitated reinstitution of antibiotics and/or oral steroids. RESULTS: Thirty-six of the 40 patients improved either symptomatically, radiographically, or both following the medical regimen. Twenty-six patients had sustained symptomatic benefit beyond 8 weeks after initial treatment. A statistically significant correlation was found between the change in pre- to posttreatment symptom scores and computed tomography scores. Using a log-rank test to compare rates of sinusitis relapse, nasal polyposis and a history of sinus surgery were significantly associated with earlier relapse (p = 0.006 and 0.018, respectively). In contrast, atopy, asthma, and persistent obstruction of the ostiomeatal unit were not associated with early relapse. CONCLUSION: Intensive medical treatment resulted in symptomatic and radiographic improvement in chronic sinusitis, and the majority of patients remained free of a relapse for >8 weeks. A history of nasal polyposis or previous sinus surgery was associated with earlier relapse of sinusitis symptoms. In contrast, the presence of atopy, a history of asthma, or persistent OMU obstruction was not associated with earlier relapse. Although long-term benefits have not been established, a prospective study of treatment outcomes from intensive medical treatment appears to be warranted.

Administration, Intranasal↗